1. Field of Invention
The present invention relates generally to methods for producing composite particles and, more particularly, to methods for producing composite particles using supercritical fluid as a plasticizing agent and an extracting agent.
2. Description of Related Art
Several processing techniques utilize the enhanced mass-transfer properties and benign nature of supercritical or near-critical fluids and/or compressed gases (hereinafter collectively referred to as “supercritical fluid”) for manufacturing composite or single-material particles. Three such processing techniques are sometimes referred to in the art as: Rapid Expansion of Supercritical Solution (RESS); Particles from Gas-Saturated Solutions (PGSS); and Supercritical Anti-Solvent (SAS).
RESS involves the precipitation of particulate material by dissolving the material in supercritical fluid to form a solution, and expanding the solution across a pressure drop. RESS usage is thus limited to compounds with a significant solubility in the supercritical fluid (typically higher than 10−4 mole fraction). Most common carrier materials that are used or desirable for coating biologically active materials are practically insoluble in supercritical fluid. Hence, the RESS technique is generally not well suited for forming uniformly coated composite particles for such applications.
The conventional SAS technique involves the dissolving of a solute in a solvent to form a solution, and then precipitation of the solute from the solution where supercritical fluid is used to extract the solvent from the solution. The SAS technique can produce generally uniform particles of various pharmaceutical materials. But, a disadvantage to this SAS technique is that sometimes it is difficult to prepare some composite particles. For example, the particles in some SAS processes precipitate as intimate mixtures rather than encapsulates. Further, some polymers precipitated by supercritical fluid extraction (SAS) agglomerate to form undesirably large particles or particles having an undesirably broad particle size distribution. Further, the solute loading of carrier material is sometimes limited by process constraints. That is, higher loading efficiencies can be difficult to achieve using this process.
With reference to the conventional PGSS technique, there can be an undesirable level of difficultly in particle production. For example, it is known that an increased viscosity and an uneven size distribution of a core material can lead to non-uniform blends of a carrier material and the core material. Thus, high viscosities and uneven size distributions can result in an inefficient coating of the core material by the carrier material, and particles thus formed have a broad size distribution. Other effects such as demixing and poor wetting can add to the difficulty of particle production using this method. Demixing and poor wetting can reduce the coating efficiency between, for example, the carrier material and the core material, which can cause an undesirable inhomogeneous particle coating.